Kazuhiko Koike1, Kazuaki Suyama2, Hiroshi Ito2, Hiroshi Itoh3, Wataru Sugiura4. 1. Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. 2. Medicines Development, GlaxoSmithKline K.K., Tokyo, Japan. 3. Biomedical Data Sciences, GlaxoSmithKline K.K., Tokyo, Japan. 4. Medical Affairs, GlaxoSmithKline K.K., Tokyo, Japan.
Abstract
AIM: The study aimed to evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) and entecavir hydrate (ETV) in nucleos(t)ide analog (NA)-naïve Japanese chronic hepatitis B (CHB) patients. METHODS: This multicenter, randomized, double-blinded study assessing the efficacy and safety of TDF 300 mg and ETV 0.5 mg in NA-naïve CHB subjects was carried out from November 2011 to November 2014, and funded by GlaxoSmithKline. The subjects were assigned to the TDF arm or ETV arm in a 2:1 ratio. The primary efficacy endpoint was the non-inferiority of TDF to ETV at week 24. RESULTS: A total of 166 subjects (TDF arm, 110; ETV arm, 56) were enrolled. The change (mean ± SE) in serum hepatitis B virus (HBV)-DNA levels from baseline to week 24 was -4.63 ± 0.044 and -4.50 ± 0.063 log10 copies/mL in the TDF and ETV arms, respectively, indicating the non-inferiority of TDF to ETV (P < 0.0001). The proportion of subjects with undetectable HBV-DNA increased from 54 to 77% and 39 to 66% in the TDF and ETV arms with continuation of the treatment from week 24 to 48, respectively. Reduction in hepatitis Bsurface antigen level was greater in subjects with hepatitis B envelope antigen (+) and high alanine aminotransferase levels (≥80 IU/L). Prevalence of drug-related adverse events at week 48 was 20% and 18% in the TDF and ETV arms, respectively. CONCLUSIONS: The study is the first to report that TDF has non-inferiority to ETV in treatment effectiveness (lowering of serum HBV-DNA level) at week 24. ClinicalTrials.gov trial registration nos. NCT01480284 and GSK LOC115409.
RCT Entities:
AIM: The study aimed to evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) and entecavir hydrate (ETV) in nucleos(t)ide analog (NA)-naïve Japanese chronic hepatitis B (CHB) patients. METHODS: This multicenter, randomized, double-blinded study assessing the efficacy and safety of TDF 300 mg and ETV 0.5 mg in NA-naïve CHB subjects was carried out from November 2011 to November 2014, and funded by GlaxoSmithKline. The subjects were assigned to the TDF arm or ETV arm in a 2:1 ratio. The primary efficacy endpoint was the non-inferiority of TDF to ETV at week 24. RESULTS: A total of 166 subjects (TDF arm, 110; ETV arm, 56) were enrolled. The change (mean ± SE) in serum hepatitis B virus (HBV)-DNA levels from baseline to week 24 was -4.63 ± 0.044 and -4.50 ± 0.063 log10 copies/mL in the TDF and ETV arms, respectively, indicating the non-inferiority of TDF to ETV (P < 0.0001). The proportion of subjects with undetectable HBV-DNA increased from 54 to 77% and 39 to 66% in the TDF and ETV arms with continuation of the treatment from week 24 to 48, respectively. Reduction in hepatitis B surface antigen level was greater in subjects with hepatitis B envelope antigen (+) and high alanine aminotransferase levels (≥80 IU/L). Prevalence of drug-related adverse events at week 48 was 20% and 18% in the TDF and ETV arms, respectively. CONCLUSIONS: The study is the first to report that TDF has non-inferiority to ETV in treatment effectiveness (lowering of serum HBV-DNA level) at week 24. ClinicalTrials.gov trial registration nos. NCT01480284 and GSK LOC115409.
Authors: William W L Wong; Petros Pechivanoglou; Josephine Wong; Joanna M Bielecki; Alex Haines; Aysegul Erman; Yasmin Saeed; Arcturus Phoon; Mina Tadrous; Mona Younis; Noha Z Rayad; Valeria Rac; Harry L A Janssen; Murray D Krahn Journal: Syst Rev Date: 2019-08-19
Authors: Ka Shing Cheung; Lung Yi Mak; Sze Hang Liu; Ho Ming Cheng; Wai Kay Seto; Man Fung Yuen; Ching Lung Lai Journal: Clin Transl Gastroenterol Date: 2020-10 Impact factor: 4.396